Tempol and perindopril protect against lipopolysaccharide-induced cognition impairment and amyloidogenesis by modulating brain-derived neurotropic factor, neuroinflammation and oxido-nitrosative stress

Abstract

We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg, i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups. A behavioral study was conducted to evaluate spatial and nonspatial memory in mice, followed by a biochemical study involving assessment of brain levels of Aβ and BDNF as Alzheimer and neuroplasticity markers; tumor necrosis factor-alpha (TNF-α), nitric oxide end-products (NOx), neuronal nitric oxide synthase (nNOS), and inducible nitric oxide synthase (iNOS) as inflammatory markers; and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione reduced (GSH), and nitrotyrosine (NT) as oxido-nitrosative stress markers. Finally, histopathological examination of cerebral cortex, hippocampus, and cerebellum sections was performed using both routine and special staining. Tempol and perindopril improved spatial and nonspatial memory in mice without affecting locomotor activity; decreased brain Aβ deposition and BDNF depletion; decreased brain TNF-α, NOx, nNOS, iNOS, MDA, and NT levels; and increased brain SOD and GSH contents, parallel to confirmatory histopathological findings. Tempol and perindopril may be promising agents against AD progression via suppression of Aβ deposition and BDNF decline, suppression of TNF-α production, support of brain antioxidant status, and amelioration of oxido-nitrosative stress and NT production.

Intracerebroventricular tempol administration in older rats reduces oxidative stress in the hypothalamus but does not change STAT3 signalling or SIRT1/AMPK pathway

“…Tempol treatment significantly increased brain antioxidant capacity in the older rats, whereas a slight, nonsignificant increase was observed in SOD. Other researchers have shown that tempol treatment was effective in increasing SOD activity and GSH activity in young brains (Ali et al 2016). However, our findings did not confirm any increase in antioxidant enzymes in either the brain or the hypothalamus.…”

Inducible nitric oxide inhibitor aminoguanidine, ameliorates deleterious effects of lipopolysaccharide on memory and long term potentiation in rat

“…Lipopolysaccharide (LPS) as a potent bacterial endotoxin, triggers production of inflammatory cytokines such as TNF-α induces ROS production [5]. On the other hand, LPS was recently reported to be able to cause amyloidogenesis in the hippocampal formation and has been used to induce an animal model of AD when it was administered to normal and transgenic rodents [6]. It has also been well documented Aβ induced LTP impairment is mediated by activation of iNOS [7].…”

Quillaja saponaria bark saponin protects Wistar rats against ferrous sulphate-induced oxidative and inflammatory liver damage

“… 2016 ) and neurodegeneration (Ali et al. 2016b ). We may conclude that Quillaja saponaria bark saponin is a promising hepatoprotective agent acting, at least partly, through scavenging free radicals and downregulation of nitric oxide production.…”